The world’s newest and most complex DNA-based computer, MAYA-II, can now play a complete version of tic-tac-toe, and never lose. Though it’s unlikely that laptops will ever run on DNA, the game’s creators in the Department of Medicine’s Division of Experimental Therapeutics say that, in the future, similar computers may roam through the bloodstream, detecting and destroying cancer cells. MAYA-II is made out of 128 different man-made DNA molecules, called logic gates, which calculate the best response to moves made by a human opponent. To make a move, the human player pipettes a short strand of DNA corresponding to the move into a 3 by 3 array of micro-plate wells that represent the game board. The way the strand binds to some logic gates, but not to others, allows MAYA-II to calculate its best move.The complexity of MAYA-II has broken though a psychological barrier in the field, says MAYA-II’s inventor Milan Stojanovic, Ph.D., assistant professor of medicine. “People tend to believe you can’t do complex calculations with DNA molecules because there is a lot of crosstalk between the molecules, but we didn’t see that in MAYA-II,” Dr. Stojanovic says.“It’s a significant achievement because of the sheer scale of the device,” says co-inventor Joanne Macdonald, Ph.D., associate research scientist. “Using more than 100 logic gates is similar to the invention of the first silicon microchips. MAYA-II proves DNA is a good medium for computation.” Though it will never be as powerful as silicon-based computers, DNA-based computation has a big advantage over silicon in wet, biological situations where DNA will not short-circuit. Dr. Macdonald sees DNA computation as the perfect way to more rapidly identify viruses. “In virus identification, you can use sequencing or microarrays. Both are expensive and require additional analysis to get an answer,” Dr. Macdonald says. “With logic gates, all the analysis occurs within the well, which can reduce the complexity of the results.”As a cancer therapy, Dr. Stojanovic envisions five or six DNA logic gates could be combined to detect and kill cancerous cells while leaving normal cells alone. He is currently designing such molecules that would distinguish cells by their cell surface proteins and deliver a toxic drug to the cancerous cells.Nano Letters; 2006; ASAP Web Release Date: 07-Oct-2006. The research was supported by the National Science Foundation and a Searle Fellowship.